Michalopoulos and Falagas Life of Rigorous Care 2011, 1: 35 http://www.annalsofintensivecare.com/content/1/1/30

REVIEW

Open Access

Colistin: new data upon pharmacodynamics

properties and clinical efficacy in critically sick

patients

Argyris S Michalopoulos1, 2 and Matthew Elizabeth Falagas2, 3, 4*

Fuzy

Recent scientific studies performed in a many patients confirmed that colistin " forgotten” for several decades revived for the supervision of attacks due to multidrug-resistant (MDR) Gram-negative bacteria (GNB) and had acceptable effectiveness and considerably less toxicity than that reported in old publications. Colistin is a swiftly bactericidal antimicrobial agent that possesses a tremendous postantibiotic effect against MDR Gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The optimal colistin dosing strategy against MDR GNB remains unknown in the intensive treatment unit (ICU) setting. A much better understanding of the pharmacokinetic-pharmacodynamic romance of colistin is urgently needed to identify the optimal dosage regimen. Though pharmacokinetic and pharmacodynamic data in ICU patients happen to be scarce, new evidence implies that the pharmacokinetics/pharmacodynamics of colistimethate sodium and colistin in critically sick patients vary from those recently found in different groups, including cystic fibrosis patients. The AUC: MIC ratio continues to be found to be the parameter best associated with colistin efficacy. To increase the AUC: MIC percentage, higher amounts of colistimethate sodium and alterations in the dosing times may be warranted in the ICU setting. Additionally , the development of colistin resistance have been linked to inadequate colistin dosage. This enforces the importance of colistin dosage optimization in critically sick patients. Although higher colistin doses seem to be beneficial, deficiency of colistin pharmacokinetic-pharmacodynamic data ends in difficulty pertaining to the optimization of daily colistin dose. In conclusion, even though colistin seems to be a very trustworthy alternative for the administration of deadly nosocomial attacks due to MDR GNB, it ought to be emphasized that there is a lack of recommendations regarding the suitable management of the infections plus the appropriate colistin doses in critically ill patients with and without multiple organ failing.

Colistin's pharmacodynamic properties

Colistimethate sodium (CMS) is an inactive prodrug of

colistin that shows a low degree of protein capturing. It is not stable in vitro and in vivo and is hydrolyzed in

individual plasma, making a complex combination of partially

sulphomethylated derivatives while using potential to generate up to thirty-two different items, including colistin [1]. After operations of CMS, colistin shows up in sang

rapidly. Colistin is approximately 50 percent bound to man

plasma. Maximum serum levels after 4 (i. versus. ) government are accomplished within 12 min. They will appeared

* Correspondence: meters. [email protected] grms

2

Alfa Institute of Biomedical Savoir (AIBS), on the lookout for Neapoleos Streets, 151 3 Marousi, Greece

Full list of author data is available towards the end of the document

higher but declined quicker than those accomplished

after i. meters. administration [2].

Colistin (base) is more active than CMS. Serum halflife of CMS is around 1 . 5-2 hours (h) after i. v. administration and 2 . 75 to 3 l after i. m. administration

in healthy subject matter, whereas serum half-life pertaining to CMS

given i. v. is more than 4 h. Old information have recommended that colistin is inadequately distributed to the pleural cavity, lung parenchyma, bones, and cerebrospinal liquid

(CSF) (15% to 25%).

CMS is eliminated mostly by the kidneys. It

should be noted any time CMS my spouse and i. v. administration,

approximately 60 per cent of CMS is excreted unchanged in

the urine via glomerular filtration during the first 24 h.

In renal failing, the reniforme excretion of CMS is decreased

making higher change...

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